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Front. Microbiol. | doi: 10.3389/fmicb.2018.02820

A New Phylogenetic Framework for the Animal-adapted Mycobacterium tuberculosis Complex

  • 1Swiss Tropical and Public Health Institute, Switzerland
  • 2Universität Basel, Switzerland
  • 3Centro Nazionale di Referenza per la Tubercolosi Bovina, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna Bruno Ubertini (IZSLER), Italy
  • 4SAMRC Centre for TB Research; DST/NRF Centre of Excellence for Biomedical Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa
  • 5Department of Biosystems Science and Engineering, ETH Zürich, Switzerland
  • 6Infectious Diseases and Immunity in Global Health, McGill University Health Centre Research Institute, The McGill International TB Centre, Canada
  • 7Victoria Infectious Diseases Reference Laboratory,Mycobacterium Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Australia
  • 8Institute for Integrative Systems Biology (I2SysBio), University of Valencia, Spain

Tuberculosis (TB) affects humans and other animals and is caused by bacteria from the Mycobacterium tuberculosis complex (MTBC). Previous studies have shown that there are at least nine members of the MTBC infecting animals other than humans; these have also been referred to as ecotypes. However, the ecology and the evolution of these animal-adapted MTBC ecotypes are poorly understood. Here we screened 12,886 publicly available MTBC genomes and newly sequenced 17 animal-adapted MTBC strains, gathering a total of 529 genomes of animal-adapted MTBC strains. Phylogenomic and comparative analyses confirm that the animal-adapted MTBC members are paraphyletic with some members more closely related to the human-adapted Mycobacterium africanum Lineage 6 than to other animal-adapted strains. Furthermore, we identified four main animal-adapted MTBC clades that might correspond to four main host shifts; two of these clades are proposed to reflect independent cattle domestication events. Contrary to what would be expected from an obligate pathogen, MTBC nucleotide diversity was not positively correlated with host phylogenetic distances, suggesting that host tropism in the animal-adapted MTBC seems to be driven more by contact rates and demographic aspects of the host population rather than host relatedness. By combining phylogenomics with ecological data, we propose an evolutionary scenario in which the ancestor of Lineage 6 and all animal-adapted MTBC ecotypes was a generalist pathogen that subsequently adapted to different host species. This study provides a new phylogenetic framework to better understand the evolution of the different ecotypes of the MTBC and guide future work aimed at elucidating the molecular mechanisms underlying host specificity

Keywords: Host-Pathogen Interactions, specificity, Host range, genetic diversity, Whole-genome sequencing

Received: 02 Aug 2018; Accepted: 02 Nov 2018.

Edited by:

Haiwei Luo, School of Life Sciences, The Chinese University of Hong Kong, China

Reviewed by:

Robson F. De Souza, Universidade de São Paulo, Brazil
Ana M. Guimaraes, Universidade de São Paulo, Brazil
Djaltou ABOUBAKER OSMAN, Center of Study and Research of Djibouti (CERD), Ethiopia
Javier Bezos, Complutense University of Madrid, Spain  

Copyright: © 2018 Brites, Loiseeau, Menardo, Borrell, Boniotti, Warren, Dippenaar, Parsons, Beisel, Behr, Fyfe, Coscolla and Gagneux. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Daniela Brites, Swiss Tropical and Public Health Institute, Basel, Switzerland,